Our long-range objective is to determine the three-dimensional structures of biologically and medically relevant proteins of the vascular system. These proteins are involved in the transport and recycling of vital raw materials in the body. X-ray crystallographic techniques will be applied to the hemoglobin-haptoglobin complex. Crystals have already been obtained and preliminary unit cell parameters have been determined. Heavy atom derivatives will be prepared and solved by utilizing our knowledge of hemoglobin. Electron density maps will be calculated showing the structure of the complex, the interaction sites of the two proteins, and any modifications in the conformation of the hemoglobin molecule. The structure will provide new evidence about the function of haptoglobin and may help explain the elevated haptoglobin levels in heart disorders and cancers. Taking advantage of the known structure of hemoglobin, Patterson search techniques and direct methods will be tried on the complex in order to develop new methods of solving protein crystal structures. An automated system for interpreting protein electron density maps is being developed using a combination of basic pattern recognition methods and fundamental principles of protein structure. The system predicts atomic coordinates for the main chain atoms and identifies and builds secondary structure regions. The system will eventually allow the crystallographer to interpret his maps very quickly and thus be able to correlate the structure with the functionally and clinically important properties very much faster. BIBLIOGRAPHIC REFERENCES: Automated Interpretation of Electron Density Maps of Proteins: A Note on Alpha-Helical Region, J. Greer, J. Mol. Biol. 98, 649-653 (1975). Automated Interpretation of Electron Density Maps of Proteins: Derivation of Atomic Coordinates for the Main Chain, J. Greer, J. Mol. Bio. (1976) 100, in press.